In the pharmaceutical industry, fine dry powders, particularly those intended for inhalation products can be packaged or “filled” directly into inhalers or indirectly into packages that can then be accessed by the delivery mechanisms of the inhalers at the point of use. Generally described, known single and multiple dose dry powder inhaler devices (“DPI's”) use (a) individual pre-measured doses, such as capsules or blisters containing the drug, which can be inserted into the device prior to dispensing, or (b) bulk powder reservoirs which are configured to administer successive quantities of the drug to the patient via a dispensing chamber which dispenses the proper dose. See generally Prime et al., Review of Dry Powder Inhalers, 26 Adv. Drug Delivery Rev., pp. 51-58 (1997); and Hickey et al., A new millennium for inhaler technology, 21 Pharm. Tech., n. 6, pp. 116-125 (1997).
Thus, depending on the filling container, the filling may be carried out to generate multi-dose amounts or unit (single) dose amounts. To assure dose uniformity and regulatory compliance, the powders should be filled in a manner that provides precisely meted or metered amounts so that an accurate active dose is delivered to the patient. Presently, dry particle excipients or additives are added to the active dry powder constituent(s) to attempt to allow for ease of filling. Present single or unit dose powder quantities typically range from about 10-30 mg. The lower range of the filling dose amount may be limited by the filling protocols available. That is, dry powders have relatively poor flow properties making precise filling problematic.
Many conventional filling methods use hoppers that have been modified to attempt to aid the flow of powder from the hopper to the target fill device. The metering of the dry powder during filling may be provided generally volumetrically, as described in U.S. Pat. No. 6,226,962, and U.S. Pat. No. 6,357,490. Additional examples of volumetric metering systems are described in U.S. Pat. Nos. 5,865,012 and 6,267,155; these volumetric metering systems propose using an oscillating filling head and/or vibration to aid powder fluidization of pharmaceutically relevant quantities. Others propose injecting a gaseous medium, such as compressed air, to facilitate the filling process, such as described in U.S. Pat. No. 5,727,607. However, this filling process uses gravimetric metering that is typically not feasible for pharmaceutical products that generally include reduced amounts (milligram quantities or less) of dry powder. The above-referenced patents are incorporated by reference as if recited in full herein.
Many pharmaceutical dry powder formulations employ small particles in the dry powder drug mixture; these small particles can be subject to forces of agglomeration and/or cohesion (i.e., certain types of dry powders are susceptible to agglomeration, which is typically caused by particles of the drug adhering together), which can result in poor flow and non-uniform dispersion, thus inhibiting reliable filling. In addition, many of these dry powder drugs are hygroscopic in nature, a characteristic that may also inhibit reliable filling. Further, fine or low-density dry powders have a tendency to float or spontaneously aerosolize during dispensing, inhibiting a uniform flow and/or making precision meted or metered dispensing problematic. Hence, it is believed that conventional dispensing methods may have about 15-20% variability, dose to dose.
Notwithstanding the above, there remains a need to provide improved and/or accurate or precise dry powder dispensers and/or dispensing systems that can reliably dispense small quantities of dry powders.